Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation is required for oral to inhalation route as there is no long-term inhalation study available.

The dose descriptor starting point was the NOAEL of 1000 mg/kg bw/day for general systemic toxicity, obtained from a combined one-generation reproduction/sub-chronic toxicity study in rats (OECD 408 & 415).

The corrected dose descriptor (NOAEC) for inhalation was calculated in accordance with the ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health. It is assumed that oral absorption of the substance is half that of inhalation absorption.

The conversion of an oral rat NOAEL into a corrected inhalatory NOAEC to assess human inhalatory exposure was performed using the modification of starting point equation as given in Figure R. 8-3 (see below) for workers (assuming an 8-hour exposure/day).

As the dose descriptor is the NOAEL, the default assessment factor is 1.

AF for differences in duration of exposure:

2

Justification:

To account for using PoD taken from a subchronic study to calculate a chronic DNEL.

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling is usually not applied in the derivation of the inhalation DNEL.

AF for other interspecies differences:

2.5

Justification:

Default AF for remaining interspecies differences

AF for intraspecies differences:

5

Justification:

To account for intraspecies differences in an occupational setting.

AF for the quality of the whole database:

1

Justification:

The database has a good quality, taking into account completeness, consistency and the standard information requirements, therefore the default factor of 1 applies.

AF for remaining uncertainties:

1

Justification:

There are no remaining uncertainties identified therefore not applicable.

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

35.24 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

25

DNEL extrapolated from long term DNEL

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

10 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Dose descriptor starting point:

NOAEL

DNEL value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

DNEL value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation is required for oral to dermal route as there is no long-term dermal study available.

The dose descriptor starting point was the NOAEL of 1000 mg/kg bw/day for general systemic toxicity, obtained from a combined one-generation reproduction/sub-chronic toxicity study in rats (OECD 408 & 415).

The corrected dose descriptor (NOAEL) for dermal exposure was calculated in accordance with the ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health.

The conversion of an oral rat NOAEL into a corrected dermal NOAEL to assess human dermal exposure was performed using the modification of starting point equation as given in Figure R. 8-3 (see below) for workers (assuming an 8-hour exposure/day).

Dermal N(L)OAEL=oral (N(L)OAEL*( ABSoral/ABSdermal)

= 1000 x (1/1)

AF for dose response relationship:

1

Justification:

As the dose descriptor is the NOAEL, the default assessment factor is 1.

AF for differences in duration of exposure:

2

Justification:

To account for using PoD taken from a subchronic study to calculate a chronic DNEL.

AF for interspecies differences (allometric scaling):

4

Justification:

Allometric scaling to account for differences in allometry in using the rat as a test model.

AF for other interspecies differences:

2.5

Justification:

Default factor.

AF for intraspecies differences:

5

Justification:

To account for intraspecies differences in an occupational setting.

AF for the quality of the whole database:

1

Justification:

The database has a good quality, taking into account completeness, consistency and the standard information requirements, therefore the default factor of 1 applies.

AF for remaining uncertainties:

1

Justification:

There are no remaining uncertainties identified therefore not applicable.

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

10 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

DNEL extrapolated from long term DNEL

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

8.69 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

50

Dose descriptor starting point:

NOAEL

DNEL value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

DNEL value:

434.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

In the absence of a repeated dose toxicity study conducted via the inhalation route of exposure the use of a PoD using the oral route of exposure has been employed. The NOAEL is taken from repeat dose oral toxicity studies in rats. It is assumed that oral absorption of the substance is half that of inhalation absorption.

As the dose descriptor is the NOAEL, the default assessment factor is 1.

AF for differences in duration of exposure:

2

Justification:

To account for using PoD taken from a subchronic study to calculate a chronic DNEL.

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling is usually not applied in the derivation of the inhalation DNEL.

AF for other interspecies differences:

2.5

Justification:

Default factor.

AF for intraspecies differences:

10

Justification:

To account for intraspecies differences.

AF for the quality of the whole database:

1

Justification:

The database has a good quality, taking into account completeness, consistency and the standard information requirements, therefore the default factor of 1 applies.

AF for remaining uncertainties:

1

Justification:

There are no remaining uncertainties identified therefore not applicable.

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

8.69 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

50

DNEL extrapolated from long term DNEL

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

200

Dose descriptor starting point:

NOAEL

DNEL value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

DNEL value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

In the absence of a repeated dose toxicity study conducted via the dermal route of exposure the use of a PoD using the oral route of exposure has been employed. The dose descriptor starting point was the NOAEL of 1000 mg/kg bw/day for general systemic toxicity, obtained from a combined one-generation reproduction/sub-chronic oral toxicity study in rats (OECD 408 & 415).

The corrected dose descriptor (NOAEL) for dermal exposure was calculated in accordance with the ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health.

The conversion of an oral rat NOAEL into a corrected dermal NOAEL to assess human dermal exposure was performed using the modification of starting point equation as given in Figure R. 8-3 (see below) for the general population.

Dermal N(L)OAEL=oral (N(L)OAEL*( ABSoral/ABSdermal)

= 1000 x (1/1)

AF for dose response relationship:

1

Justification:

As the dose descriptor is the NOAEL, the default assessment factor is 1.

AF for differences in duration of exposure:

2

Justification:

To account for using PoD taken from a subchronic study to calculate a chronic DNEL.

AF for interspecies differences (allometric scaling):

4

Justification:

Allometric scaling to account for differences in allometry in using the rat as a test model.

AF for other interspecies differences:

2

Justification:

Default factor.

AF for intraspecies differences:

10

Justification:

To account for intraspecies differences.

AF for the quality of the whole database:

1

Justification:

The database has a good quality, taking into account completeness, consistency and the standard information requirements, therefore the default factor of 1 applies.

AF for remaining uncertainties:

1

Justification:

There are no remaining uncertainties identified therefore not applicable.

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

200

DNEL extrapolated from long term DNEL

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

200

Dose descriptor starting point:

NOAEL

DNEL value:

1 000 mg/kg bw/day

AF for dose response relationship:

1

Justification:

As the dose descriptor is the NOAEL, the default assessment factor is 1.

AF for differences in duration of exposure:

2

Justification:

To account for using PoD taken from a subchronic study to calculate a chronic DNEL.

AF for interspecies differences (allometric scaling):

4

Justification:

Allometric scaling to account for differences in allometry in using the rat as a test model.

AF for other interspecies differences:

2.5

Justification:

Default factor.

AF for intraspecies differences:

10

Justification:

To account for intraspecies differences.

AF for the quality of the whole database:

1

Justification:

The database has a good quality, taking into account completeness, consistency and the standard information requirements, therefore the default factor of 1 applies.

AF for remaining uncertainties:

1

Justification:

There are no remaining uncertainties identified therefore not applicable.

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

200

DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

There are no identified uses in the public domain however DNEL values for the General Population have been calculated to support the assessment of man via the environment.

Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.

Route: .live2

Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.

Do not show this message again

This website uses cookies to ensure you get the best experience on our websites.